5-Fluorouracil (5-FU) is widely used in cancer patients to treat tumors including, but not limited to, colorectal, head and neck, stomach and breast carcinomas. 5-FU is most often administered systemically, but is also applied topically to treat some forms of pre-cancerous and cancerous skin disorders. Prodrugs of 5-FU are also used in cancer treatment.
5-FU pharmacokinetics have been shown to have a wide interpatient and intrapatient variability. There are still several uncertainties surrounding the rates of metabolism of 5-FU between individuals, including differences between regulated doses among patients. For example, when equal doses of 5-FU, prepared based on calculated body surface area per individual, are administered to different patients, marked differences in systemic exposures occurs. (Bertino et al., Clin. Colorectal Cancer, 6:407-426, (2007)). This can lead to toxicity as a result of overdosing in some patients, or reduced efficacy due to underdosing in others. Additionally, some patients have a dihydropyrimidine dehydrogenase (DPD) deficiency, which can cause very severe, possibly lethal, toxic side-effects from 5-FU exposure. In fact, some patients, particularly geriatric patients, have reduced 5-FU plasma clearance which leads to a higher risk of toxicity.
Accordingly, it is critical to design effective routine therapeutic drug management systems for administering and monitoring the levels of 5-FU in the body so that the toxic or ineffective doses can be adjusted in a timely manner to limit and avoid any undesired side-effects in patients. For example, the ability to individualize dose adjustments of 5-FU to a target plasma level would be more accurate and preferred to a method of dosing based on body surface area. Individualized dosing would also lead to decreased incidents of toxicity, improved survival rates and increased overall response of patients to the 5-FU treatment. There exists a need for improved antibodies, immunoassays and methods for monitoring 5-FU levels so that 5-FU doses can be adjusted to achieve optimal plasma concentrations.